Effects of Phorbol Esters and Forskolin on Basal and Histamine‐induced Accumulation of Inositol Phosphates in Cultured Bovine Adrenal Chromaffin Cells
- 5 October 1989
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 53 (4), 1219-1227
- https://doi.org/10.1111/j.1471-4159.1989.tb07418.x
Abstract
The effect of phorbol esters and forskolin pretreatment on basal and histamine-induced accumulation of inositol phosphates and catecholamine release was examined in cultures of bovine adrenal chromaffin cells. Histamine caused a dose-dependent, Ca2+-dependent accumulation of total inositol phosphates wit an EC50 at .apprx.1 .mu.M and an eight- to 10-fold increase at 100 .mu.M within 30 min of incubation. Histamine (10 .mu.M) also caused the release of cellular catecholamines amounting to some 2.8% of cellular stores released over a 20-min period. Both the inositol phosphate and catecholamine responses were completely blocked by the H1-antagonist mepyramine and were insensitive to the H2-antagonist cimetidine. Examination of the time course of accumulation of the individual inositol phosphates stimulated by histamine revealed an early and sustained rise in inositol 1,4-bisphosphate content but not inositol 1,4,5-trisphosphate content at 1 min and the overall largest accumulation of inositol monophosphate after 30 min of stimulation. Pretreatment with the tumor-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA) resulted in a dose-dependent, time-dependent inhibition of histamine-induced inositol phosphate formation and catecholamine secretion. In this inhibitory action, PMA exhibited high potency (IC50 of .apprx. 0.5 nM), an effect not shared by the inactive phorbol ester 4-.alpha.-phorbol 12,13-didecanoate. Pretreatment with forskolin, on the other hand, only marginally inhibited the histamine-induced inositol phospholipid metabolism and catecholamine secretion. These data suggest that protein kinase C activation in chromaffin cells may mediate a negative feedback control on inositol phospholipid metabolism.Keywords
This publication has 53 references indexed in Scilit:
- Stimulation-Evoked Ca2+Fluxes in Cultured Bovine Adrenal Chromaffin Cells Are Enhanced by ForskolinJournal of Neurochemistry, 1987
- Differential effects of protein kinase C activators on carbamylcholine- and high K+-induced rises in intracellular free calcium concentration in cultured adrenal chromaffin cellsBiochemical and Biophysical Research Communications, 1986
- H1-Histaminergic activation stimulates inositol-1-phosphate accumulation in chromaffin cellsBiochemical and Biophysical Research Communications, 1986
- Protein kinase C mediated regulation of calcium channels in PC-12 pheochromocytoma cellsBiochemical and Biophysical Research Communications, 1986
- Inositol Trisphosphate Mobilizes Intracellular Calcium in Permeabilized Adrenal Chromaffin CellsJournal of Neurochemistry, 1986
- Cholinergic Receptor‐Mediated Phosphorylation and Activation of Tyrosine Hydroxylase in Cultured Bovine Adrenal Chromaffin CellsJournal of Neurochemistry, 1986
- Phorbol ester stimulates catecholamine synthesis in isolated bovine adrenal medullary cellsFEBS Letters, 1985
- The phorbol ester TPA enhances A23187- but not carbachol-and high K+-induced catecholamine secretion from cultured bovine adrenal chromaffin cellsBiochemical and Biophysical Research Communications, 1985
- Tumor promoter phorbol 12-myristate, 13-acetate inhibits phosphoinositide hydrolysis and cytosolic Ca2+ rise induced by the activation of muscarinic receptors in PC12 cellsBiochemical and Biophysical Research Communications, 1985
- Muscarinic Receptors in Chromaffin Cell Cultures Mediate Enhanced Phospholipid Labeling but Not Catecholamine SecretionJournal of Neurochemistry, 1981